Epidermal cells differentiate as they move toward the surface. Certain cellular organelles, such as keratohyalin granules, thickened plasma membrane, membrane coating granules, etc., are formed in cells during this process. The chemical nature of these structures is not known as they have not yet been isolated selectively. Therefore, techniques of electron and light microscopic autoradiography after injection of tritiated amino acids and lipid precursors and of cytochemistry have been used in this project to study chemical substances involved in the formation of these structures. The results reveal that additional proteins are synthesized in granular cells besides protein(s) formed in the lower layers. Protein which is rich in histidine contributes to the formation of keratohyalin granules, whereas cystine protein is added to the plasma membrane to thicken it. We are developing suitable techniques to isolate and characterize proteins synthesized in differentiated epidermal cells. Immunohistochemical techniques will be employed to determine localization of these proteins in the epidermis. We believe that changes in chemical composition of these structures reflect upon the morphology observed in skin diseases, such as psoriasis, ichthyosis and other hyperkeratoses. Information will be applied to understand the pathogenesis of these diseases. BIBLIOGRAPHIC REFERENCES: Stegman, S.J., Fukuyama, K. and Epstein, W.L. Inhibition of the in vivo effects of concanavalin-A on mammalian epidermis by alpha-methyl-D-glucopyranoside. J. Invest. Derm. 66:17-21, 1976. Delescluse, D., Fukuyama, K. and Epstein, W.L.: Dibutyryl cyclic amp-induced differentiation of epidermal cells in tissue culture. J. Invest. Derm. 66:8-13, 1976.